Grape seeds contain about 5-8% by weight flavonoids. Flavonoids constitute an important group of dietary polyphenolic compounds that are widely distributed in plants. More than 4000 chemically unique flavonoids have been identified in plant sources, such as fruits, vegetables, legumes, nuts, seeds, herbs, spices, flowers, as well as in beverages such as tea, cocoa, beer, wine, and grape juice.
The terminology of flavonoids with respect to grape seeds refers to monomeric flavan-3-ols, specifically (+)-catechin, (−)-epicatechin, and (−)-epicatechin 3-gallate. Two or more flavan-3-ol monomers chemically linked are called proanthocyanidins or oligomeric proanthocyanidins (“OPCs”), which includes procyanidins and prodelphinidins. OPCs containing two monomers are called dimers, three monomers are called trimers, four monomers are called tetramers, five monomers are called pentamers, etc. Operationally, the oligomers have chain lengths of 2 to 7 (dimers to heptamers); whereas polymers represent components with chain lengths greater than 7. After considerable discussion, it was the consensus of the Grape Seed Method Evaluation Committee (through the National Nutritional Foods Association) to define OPCs as all proanthocyanidins containing two or more monomers, including polymers or condensed tannins. Thus, oligomers in grape extracts include, for instance, dimers and trimers, and there is evidence that the polymers can have as many as sixteen units.
Below is a typical structure of a proanthocyanidin, showing epicatechin-gallate extension units and terminal units. The extension units are represented, for instance, by the epicatechin (2) and epigallocatechin (3) linking groups. Whereas, a terminal unit is represented by the epicatechin gallate (4) group.

In order for polyphenolic compounds to be used commercially as a grape extract, these compounds have to be separated from grapes in a more concentrated form. The general process in which the polyphenolic compounds are extracted, purified and concentrated from whole grapes, grape pomace and grape seeds is disclosed in U.S. Pat. No. 6,544,581, which is incorporated herein by reference.
In addition to antioxidant activities, flavonoids have been reported, in animal studies, to exert anti-cancer effects by reducing growth of new blood vessels, and to have anti-inflammatory, anti-microbial, and anti-allergenic activities. It has also been found that the grape extract of the present invention may be used to lower blood pressure in pre-hypertensive individuals and individuals with Metabolic Syndrome. It has also been suggested that the grape extract of the present invention will, in addition to lowering blood pressure, reduce oxidized LDL cholesterol in individuals with Metabolic Syndrome. Increased LDL cholesterol is a recognized risk factor for atherosclerosis. There is strong evidence that oxidatively modified LDL initiates the development of this pathological process. Thus, decreasing the concentration of oxidized LDL may reduce and/or prevent atherosclerosis in individuals with Metabolic Syndrome.
Pre-hypertensive individuals are classified as individuals that have systolic pressure between 120 and 139 mmHg or have diastolic pressure between 81 and 89 mmHG. This classification is based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), page 87, NIH Publication No. 04-5230. Pre-hypertensive individuals are not typically treated with drug therapy, but rather are given suggestions for a healthy lifestyle. These suggestions include maintaining a healthy weight; being physically active; following a healthy eating plan that emphasizes fruits, vegetables, and low fat dairy foods; choosing and preparing foods with less sodium; and drinking alcoholic beverages in moderation if at all. Adopting healthy lifestyle habits is usually an effective first step in both preventing and controlling abnormal blood pressure.
“Metabolic Syndrome,” also called “Syndrome X,” the “Insulin Resistance Syndrome,” or the “Deadly Quartet,” is characterized by an accumulation of risk factors for cardiovascular disease, stroke and/or diabetes mellitus type II. Metabolic Syndrome may be caused by an overproduction of cortisol, a stress hormone, which causes an accumulation of fat inside the abdominal cavity and insulin resistance. Drug therapy is not currently recommended for individuals with Metabolic Syndrome. The risk factors that characterize Metabolic Syndrome include an increased amount of adipose tissue inside the abdominal cavity (abdominal obesity), insulin resistance with increased risk of developing diabetes, hyperinsulinemia, high levels of blood fats, increased blood pressure, and elevated serum lipids. The National Cholesterol Education Adult Treatment Panel (ATP III) defined Metabolic Syndrome as individuals having at least three of the following risk factors:
Risk FactorDefining LevelAbdominal obesity, givenas waist circumference*†Men>102 cm (>40 in)Women>88 cm (>35 in)Triglycerides≧150 mg/dLHDL cholesterolMen<40 mg/DlWomen<50 mg/dLBlood pressure≧130/≧85 mm HgFasting glucose≧110 mg/dL‡*Overweight and obesity are associated with insulin resistance and Metabolic Syndrome. The presence of abdominal obesity, however, is more highly correlated with the metabolic risk factors than is an elevated BMI. Therefore, the simple measure of waist circumference is recommended to identify the body weight component of Metabolic Syndrome.†Some male patients can develop multiple metabolic risk factors when the waist circumference is only marginally increased, e.g., 94 to 102 cm (37 to 39 in). Such patients may have a strong genetic contribution to insulin resistance. They should benefit from changes in life habits, similarly to men with categorical increases in waist circumference.‡the American Diabetes Association has recently established a cut-off point of ≧100 mg/dL, above which individuals have either pre-diabetes (impaired fasting glucose) or diabetes. This new cut-off point should be applicable for identifying the lower boundary to define an elevated glucose as one criterion for Metabolic Syndrome.
Conditions related to Metabolic Syndrome include diabetes mellitus type II, dyslipoproteinemia, myocardial infarction, stroke and other arteriosclerotic diseases, as well as the risk factors for these diseases, including insulin resistance in general, abdominal obesity caused by accumulation of intra-abdominal fat, elevated blood serum lipids and glucose, raised diastolic and/or systolic blood pressure, and hypertension.
There is a need for a grape extract and a dietary supplement comprising such grape extract that can be used as adjunctive therapy, which is effective for providing health benefits such as lowering blood pressure in pre-hypertensive individuals or those with Metabolic Syndrome.